Novel biopsy procedure may offer early detection of cancer of the esophagus

Novel biopsy procedure may offer early detection of cancer of the esophagus

A 'pill on a string' could help doctors detect esophageal cancer at an early stage, helping them overcome the problem of wide variation between biopsies. This research was published in Nature Genetics (2015; doi:10.1038/ng.3357).

The Cytosponge sits within a pill that, when swallowed, dissolves to reveal a sponge that scrapes off cells when withdrawn up the esophagus. It allows doctors to collect cells from all along the esophagus, whereas standard biopsies take individual point samples.

Esophageal cancer is often preceded by Barrett's esophagus, a condition in which cells within the lining of the esophagus begin to change shape and can grow abnormally. The cellular changes are caused by acid and bile reflux, which is when the stomach juices come back up the esophagus. Of every 100 people with Barrett's esophagus, 1 to 5 of them go on to develop esophageal cancer in their lifetime, a form of cancer that can be difficult to treat, particularly if not caught early enough.

At present, Barrett's esophagus and esophageal cancer are diagnosed using biopsies, which look for signs of dysplasia, the proliferation of abnormal cancer cells.

An alternative way of spotting very early signs of esophageal cancer would be to look for important genetic changes. However, researchers have shown that variations in mutations across the esophagus mean that standard biopsies may miss cells with important mutations. A sample was more likely to pick up key mutations if taken using the Cytosponge, developed by Professor Rebecca Fitzgerald, MD, at the Medical Research Council Cancer Research Unit at the University of Cambridge in the United Kingdom.

"The trouble with Barrett's esophagus is that it looks bland and might span over 10 cm," explained Fitzgerald. "We created a map of mutations in a patient with the condition and found that within this stretch, there is a great deal of variation amongst cells. Some might carry an important mutation, but many will not. If you're taking a biopsy, this relies on your hitting the right spot. Using the Cytosponge appears to remove some of this game of chance."

Fitzgerald and colleagues carried out whole genome sequencing to analyze paired Barrett's esophagus and esophageal cancer samples taken at one point in time from 23 patients, as well as 73 samples taken over a 3-year period from one patient with Barrett's esophagus.

The researchers found patterns of mutations in the genome that provided a fingerprint of the causes of the cancer. The Cambridge team found fingerprints which they believe are likely to be due to the damage caused to the lining of the esophagus by stomach acid splashing onto its walls; the same fingerprints could be seen in both Barrett's esophagus and esophageal cancer, suggesting that these changes occur very early on the process.

Even in areas of Barrett's esophagus without cancer, the researchers found a large number of mutations in their tissue: on average 12,000 per person, compared to an average of 18,000 mutations within the cancer. Many of these are likely to have been bystanders, genetic mutations that occurred along the way but were not actually implicated in cancer.

The researchers found that there appeared to be a tipping point, where a patient would go from having lots of individual mutations, but no cancer, to a situation where large pieces of genetic information were being transferred not just between genes but between chromosomes.